Pharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy

Abstract

Abstract Background In this phase Ib multicenter study, we sought to characterize the PK, safety and tolerability of durvalumab (D), an anti-PD-L1 antibody, ± tremelimumab (T), an anti-CTLA-4 antibody, in combination with one of four standard platinum-doublet chemotherapy regimens. We will present the PK, and update overall survival data. Methods Regardless of tumour PD-L1 status, patients were enrolled into one of four cohorts: pemetrexed, gemcitabine, etoposide (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin), each of which were evaluated in one of six dose levels [Table]. Dose escalation followed a Rolling Six type design. Concurrent enrollment of cohorts was allowed. Limited PK was collected ≤1\xa0hour pre-dose and ≤10\xa0minutes post-dose on day 1 of cycles 1-3 as well as week 6 or 8 post chemotherapy. Results One hundred and thirty-six patients (median age=62 (range 30-83); males:females=67:69; ECOG PS 0/1=32%/68%). The majority of patients had non-small cell (53.7%) or small cell (13.2%) lung cancer. Immune-related adverse events (irAEs) that were considered related to D or T were mainly Table . 474P Dose Level Durvalumab Q3W Tremelimumab (with chemotherapy) Tremelimumab (after chemotherapy) 0 15mg/kg - - 1 15mg/kg 1\xa0mg/kg X 1 1-2 doses 2a 15mg/kg 1\xa0mg/kg X 3 Q6w 1-2 doses 2b 15mg/kg 3\xa0mg/kg X 1 1-2 doses Q6w 3 1125mg 56\xa0mg X 4 Q3w 56\xa0mg X 2 Q3w 4 1500mg 75\xa0mg X 4 Q3w 75\xa0mg X 1 Conclusions Standard platinum-doublet chemotherapy regimens did not alter the PK of D+T or D compared with historical monotherapy therapy data. Toxicities were manageable and were not associated with PK. Clinical trial identification NCT02537418. Legal entity responsible for the study Canadian Cancer Trials Group (CCTG). Funding AstraZeneca provided drug and partial funding to support of this Canadian Cancer Trials Group (CCTG) study. Disclosure D. Hao: Honoraria (self), Advisory Board: Roche; Honoraria (self), Advisory Board; funding for clinical trial: BMS; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: Merck; Honoraria (self), Advisory Board: BI. P.M. Ellis: Honoraria (self), Advisory / Consultancy, Advisory Board: AstraZeneca; Advisory / Consultancy, Advisory Board: Takeda; Honoraria (self), Advisory / Consultancy, Advisory Board: Abbvie; Honoraria (self): Pfizer; Honoraria (self): BMS. R.A. Juergens: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer. P.A. Bradbury: Honoraria (self), Advisory / Consultancy: Abbvie; Honoraria (self): Pfizer; Honoraria (self): Lilly; Advisory / Consultancy: BI. M. Tsao: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck. M. Tehfe: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celegen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda. C.K. Kollmannsberger: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Sanofi. J.R. Goffin: Honoraria (self), Speaker Bureau / Expert testimony, 2014, 2018: Amgen; Honoraria (self), 2015: Boehringer Ingelheim; Honoraria (self), 2015: Bristol-Myers Squibb; Honoraria (self), 2018: Merck; Travel / Accommodation / Expenses, 2017: AstraZeneca. P. Wheatley-Price: Advisory / Consultancy: Takeda; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Abbvie; Advisory / Consultancy: Roche. J. Hilton: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Puma; Advisory / Consultancy: Eli Lilly. L.K. Seymour: Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Received funding on behalf of CCTG from AstraZeneca to support the study: AstraZeneca. All other authors have declared no conflicts of interest.